Severe Hemophilia APhase 4NCT00323856
Safety Study of Alphanate in Previously Treated Patients With Severe Hemophilia A
A Phase 4 study testing Alphanate SD/HT in people with Severe Hemophilia A, run by Grifols Biologicals, LLC at 2 sites in Poland.
Trial summary
The purpose of this study is to determine the immunologic and overall safety associated with long-term use of Alphanate in subjects diagnosed with severe hemophilia A (Factor VIII:C less than 0.01 IU/ml), who have been previously treated with plasma-derived Factor VIII products other than Alphanate and who have no… Read more about this study
- Who is it for?
- Ages 6 to 65 years, men only
- Conditions the study is for
- Severe Hemophilia A
- What is being tested?
- Alphanate SD/HT
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 51 participants
- Where
- 2 sitesPoland
- Study dates
- 8 Apr 2003to 14 Dec 2018
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 65 years
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Male.
- At least 6 years of age and not more than 65 years of age.
- Signed and dated Informed Consent Form and Patient Authorization for Release of Information approved by the appropriate Institutional Review Board (IRB) prior to screening and enrollment. If the subject is a minor (i.e., less than 18 years of age) both he and his parent or legal guardian must sign and date the informed consent.
- Diagnosis of severe hemophilia A.
- Levels of Factor VIII less than 0.01 IU/mL.
- Treatment with cryoprecipitate, Factor VIII concentrates, and/or whole blood, for at least 150 cumulative exposure days (CEDs) prior to enrollment.
Show all 13Show fewer
- No treatment with cryoprecipitate, Factor VIII concentrate, or any other blood product, for at least 72 hours prior to screening.
- No previous diagnosis with inhibitors to Factor VIII at any detectable titer.
- Subjects must never have been diagnosed with nonspecific inhibitors of coagulation.
- Negative test for the presence of Factor VIII inhibitors at screening and enrollment.
- CD4 counts greater than or equal to 400 cells/µL.
- Vaccination against hepatitis A and hepatitis B, or evidence of antibodies against hepatitis A and hepatitis B. (A subject who has no prior immunity against hepatitis A will be offered a course of vaccination for hepatitis A).
- Karnofsky Performance Score of at least 50.
Who cannot join
- Any immunosuppressive medications including intravenous immunoglobulins at the time of enrollment.
- Clinical signs or symptoms of an infection, such as fever, chills or nausea during screening or enrollment.
- History of frequent reactions to Factor VIII concentrates (e.g., chills or headaches).
- Prior treatment with Alphanate® (Solvent-Detergent/ Heat-Treated).
- Immunocompromised (including HIV+ status or has an impaired immune system due to disease or treatment).
Trial locations and contacts
2 sites in 1 country.
Poland2 sites
Katedra i Klinika Hematologii Collegium Medicum UJ
Krakow
Oddzial Chorob Wewnetrznych i Hematologii
Poznan, Szkolna
About this study
Official title: Phase IV A Study of Immunologic Safety for Alphanate in Previously Treated Patients Diagnosed With Severe Hemophilia A
The purpose of this study is to determine the immunologic and overall safety associated with long-term use of Alphanate in subjects diagnosed with severe hemophilia A (Factor VIII:C less than 0.01 IU/ml), who have been previously treated with plasma-derived Factor VIII products other than Alphanate and who have no history of developing either antibody inhibitors to Factor VIII or nonspecific inhibitors of coagulation.
Read the detailed description
This is a Phase IV, non-randomized, multicenter study of at least 50 evaluable subjects diagnosed with severe hemophilia A. Enrolled subjects will be treated at home and with in-clinic therapy exclusively with Alphanate as their sole source of Factor VIII concentrate for prophylaxis and treatment of all bleeding episodes and surgical procedures. Subjects will be treated for at least 2 years and a minimum of 50 exposure days, or if 50 exposure days are not reached, for a maximum of 30 months and in accordance with the subject's usual pre-study treatment regimen. Subjects will continue treatment as above or until they develop inhibitors to Factor VIII at a titer greater than or equal to 5 Bethesda units (BU/ml); Factor VIII becomes ineffective at providing hemostasis, or the subject exhibits severe or serious adverse events that prevent completion of the study.
- Conditions
- Severe Hemophilia A
- Being tested
- Alphanate SD/HT
- Keywords
- Hemophilia A, Plasma-derived treatment, Factor VIII, Inhibitor
- Medical subject headings
- Hemophilia A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Alphanate SD/HTDrug
Also called Anti-hemophilic (human) coagulation factor VIII
Plasma-derived preparation of Factor VIII
| Study group | Role | What they receive |
|---|---|---|
| Coagulation factor VIII (Human) | Experimental | Anti-Hemophilic coagulation factor VIII (Human) Alphanate SD/HT Receives: Drug: Alphanate SD/HT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Factor VIII (FVIII) Inhibitor Development
Incidence of FVIII inhibitor development was defined as any result determined positive at a central laboratory (inhibitor titer of greater than 0.6 modified Bethesda Units/milliliters [BU/mL]) using Nijmegen modification of the Bethesda assay.
Measured: Up to Month 30
Secondary outcomes (9)
Number of Participants With Adverse Events (AE)
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a medicinal product or study treatment, and which did not necessarily have a causal relationship with this administration. Here end of study is defined as completion/discontinuation visit.
Measured: Up to Month 30
Change From Baseline in Alkaline Phosphatase
The Baseline value was the last non-missing value before study drug was taken and end of study was defined as completion/discontinuation visit. Change from Baseline was calculated by subtracting Baseline value from the post-infusion visit value.
Measured: Baseline and Quarterly Visit 1 (Month 3), 2 (Month 6), 3 (Month 9), 4 (Month 12), 5 (Month 15), 6 (Month 18), 7 (Month 21), 8 (Month 24), 9 (Month 27) and 10 (Month 30)
Change From Baseline in Alanine Aminotransferase
The Baseline value was the last non-missing value before study drug was taken and end of study was defined as completion/discontinuation visit. Change from Baseline was calculated by subtracting Baseline value from the post-infusion visit value.
Measured: Baseline and Quarterly Visit 1 (Month 3), 2 (Month 6), 3 (Month 9), 4 (Month 12), 5 (Month 15), 6 (Month 18), 7 (Month 21), 8 (Month 24), 9 (Month 27) and 10 (Month 30)
Change From Baseline in Aspartate Aminotransferase
The Baseline value was the last non-missing value before study drug was taken and end of study was defined as completion/discontinuation visit. Change from Baseline was calculated by subtracting Baseline value from the post-infusion visit value.
Measured: Baseline and Quarterly Visit 1 (Month 3), 2 (Month 6), 3 (Month 9), 4 (Month 12), 5 (Month 15), 6 (Month 18), 7 (Month 21), 8 (Month 24), 9 (Month 27) and 10 (Month 30)
Change From Baseline in Lactate Dehydrogenase
The Baseline value was the last non-missing value before study drug was taken and end of study was defined as completion/discontinuation visit. Change from Baseline was calculated by subtracting Baseline value from the post-infusion visit value.
Measured: Baseline and Quarterly Visit 1 (Month 3), 2 (Month 6), 3 (Month 9), 4 (Month 12), 5 (Month 15), 6 (Month 18), 7 (Month 21), 8 (Month 24), 9 (Month 27) and 10 (Month 30)
Change From Baseline in Bilirubin
The Baseline value was the last non-missing value before study drug was taken and end of study was defined as completion/discontinuation visit. Change from Baseline was calculated by subtracting Baseline value from the post-infusion visit value.
Measured: Baseline and Quarterly Visit 1 (Month 3), 2 (Month 6), 3 (Month 9), 4 (Month 12), 5 (Month 15), 6 (Month 18), 7 (Month 21), 8 (Month 24), 9 (Month 27) and 10 (Month 30)
Change From Baseline in Blood Urea Nitrogen
The Baseline value was the last non-missing value before study drug was taken and end of study was defined as completion/discontinuation visit. Change from Baseline was calculated by subtracting Baseline value from the post-infusion visit value.
Measured: Baseline and Quarterly Visit 1 (Month 3), 2 (Month 6), 3 (Month 9), 4 (Month 12), 5 (Month 15), 6 (Month 18), 7 (Month 21), 8 (Month 24), 9 (Month 27) and 10 (Month 30)
Change From Baseline in Creatinine
The Baseline value was the last non-missing value before study drug was taken and end of study was defined as completion/discontinuation visit. Change from Baseline was calculated by subtracting Baseline value from the post-infusion visit value.
Measured: Baseline and Quarterly Visit 1 (Month 3), 2 (Month 6), 3 (Month 9), 4 (Month 12), 5 (Month 15), 6 (Month 18), 7 (Month 21), 8 (Month 24), 9 (Month 27) and 10 (Month 30)
Number of Participants Human Immunodeficiency Virus Type 1 and 2 (HIV-1/HIV-2), Hepatitis A Virus (HAV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) or Parvovirus B19 -Negative at Baseline Who Are Seropositive for Any of These Viruses
Seroconversion based on Enzyme-linked Immunosorbent Assay (ELISA). Seronegative defined as non-reactive in an ELISA test for antibody to the virus in question. Seropositive defined as reactive in an ELISA test for antibody to the virus in question.
Measured: Up to Month 30
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2006 (estimated)
- Study start8 Apr 2003
- Primary completion11 Dec 2018
- Study completion14 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Severe Hemophilia AStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- Grifols Biologicals, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Michael Ken Woodward, Study director, Instituto Grifols SA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00323856
- Sponsor's protocol ID
- GBI 04-01
- Status last verified
- Jan 2025
- First submitted
- 8 May 2006
- Last updated
- 16 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase IV A Study of Immunologic Safety for Alphanate in Previously Treated Patients Diagnosed With Severe Hemophilia A
- ClinicalTrials.gov ID
- NCT00323856
- Acronym / sponsor ID
- GBI 04-01
- Conditions
- Severe Hemophilia A
- Keywords
- Hemophilia A, Plasma-derived treatment, Factor VIII, Inhibitor
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 51 participants (actual)
- Lead sponsor
- Grifols Biologicals, LLCIndustry (pharma, biotech, devices)
- Study start
- 8 Apr 2003 (actual)
- Primary completion
- 11 Dec 2018 (actual)
- Study completion
- 14 Dec 2018 (actual)
- First posted
- 10 May 2006 (estimated)
- Results
- Posted 9 Jun 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine the immunologic and overall safety associated with long-term use of Alphanate in subjects diagnosed with severe hemophilia A (Factor VIII:C less than 0.01 IU/ml), who have been previously treated with plasma-derived Factor VIII products other than Alphanate and who have no history of developing either antibody inhibitors to Factor VIII or nonspecific inhibitors of coagulation.
Detailed description
This is a Phase IV, non-randomized, multicenter study of at least 50 evaluable subjects diagnosed with severe hemophilia A. Enrolled subjects will be treated at home and with in-clinic therapy exclusively with Alphanate as their sole source of Factor VIII concentrate for prophylaxis and treatment of all bleeding episodes and surgical procedures. Subjects will be treated for at least 2 years and a minimum of 50 exposure days, or if 50 exposure days are not reached, for a maximum of 30 months and in accordance with the subject's usual pre-study treatment regimen. Subjects will continue treatment as above or until they develop inhibitors to Factor VIII at a titer greater than or equal to 5 Bethesda units (BU/ml); Factor VIII becomes ineffective at providing hemostasis, or the subject exhibits severe or serious adverse events that prevent completion of the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Coagulation factor VIII (Human) | Experimental | Drug: Alphanate SD/HTAnti-Hemophilic coagulation factor VIII (Human) Alphanate SD/HT |
Who may qualify
- Ages
- 6 to 65 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (13 listed)
- Male.
- At least 6 years of age and not more than 65 years of age.
- Signed and dated Informed Consent Form and Patient Authorization for Release of Information approved by the appropriate Institutional Review Board (IRB) prior to screening and enrollment. If the subject is a minor (i.e., less than 18 years of age) both he and his parent or legal guardian must sign and date the informed consent.
- Diagnosis of severe hemophilia A.
- Levels of Factor VIII less than 0.01 IU/mL.
Key exclusion criteria (5 listed)
- Any immunosuppressive medications including intravenous immunoglobulins at the time of enrollment.
- Clinical signs or symptoms of an infection, such as fever, chills or nausea during screening or enrollment.
- History of frequent reactions to Factor VIII concentrates (e.g., chills or headaches).
- Prior treatment with Alphanate® (Solvent-Detergent/ Heat-Treated).
- Immunocompromised (including HIV+ status or has an impaired immune system due to disease or treatment).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Alphanate SD/HTAlso: Anti-hemophilic (human) coagulation factor VIIIPlasma-derived preparation of Factor VIII | Drug | Coagulation factor VIII (Human) |
Primary outcome
Number of Participants With Factor VIII (FVIII) Inhibitor Development
Time frame: Up to Month 30
Incidence of FVIII inhibitor development was defined as any result determined positive at a central laboratory (inhibitor titer of greater than 0.6 modified Bethesda Units/milliliters [BU/mL]) using Nijmegen modification of the Bethesda assay.
9 secondary outcomes
Number of Participants With Adverse Events (AE)
Time frame: Up to Month 30
Change From Baseline in Alkaline Phosphatase
Time frame: Baseline and Quarterly Visit 1 (Month 3), 2 (Month 6), 3 (Month 9), 4 (Month 12), 5 (Month 15), 6 (Month 18), 7 (Month 21), 8 (Month 24), 9 (Month 27) and 10 (Month 30)
Change From Baseline in Alanine Aminotransferase
Time frame: Baseline and Quarterly Visit 1 (Month 3), 2 (Month 6), 3 (Month 9), 4 (Month 12), 5 (Month 15), 6 (Month 18), 7 (Month 21), 8 (Month 24), 9 (Month 27) and 10 (Month 30)
Change From Baseline in Aspartate Aminotransferase
Time frame: Baseline and Quarterly Visit 1 (Month 3), 2 (Month 6), 3 (Month 9), 4 (Month 12), 5 (Month 15), 6 (Month 18), 7 (Month 21), 8 (Month 24), 9 (Month 27) and 10 (Month 30)
Change From Baseline in Lactate Dehydrogenase
Time frame: Baseline and Quarterly Visit 1 (Month 3), 2 (Month 6), 3 (Month 9), 4 (Month 12), 5 (Month 15), 6 (Month 18), 7 (Month 21), 8 (Month 24), 9 (Month 27) and 10 (Month 30)
Change From Baseline in Bilirubin
Time frame: Baseline and Quarterly Visit 1 (Month 3), 2 (Month 6), 3 (Month 9), 4 (Month 12), 5 (Month 15), 6 (Month 18), 7 (Month 21), 8 (Month 24), 9 (Month 27) and 10 (Month 30)
Change From Baseline in Blood Urea Nitrogen
Time frame: Baseline and Quarterly Visit 1 (Month 3), 2 (Month 6), 3 (Month 9), 4 (Month 12), 5 (Month 15), 6 (Month 18), 7 (Month 21), 8 (Month 24), 9 (Month 27) and 10 (Month 30)
Change From Baseline in Creatinine
Time frame: Baseline and Quarterly Visit 1 (Month 3), 2 (Month 6), 3 (Month 9), 4 (Month 12), 5 (Month 15), 6 (Month 18), 7 (Month 21), 8 (Month 24), 9 (Month 27) and 10 (Month 30)
Number of Participants Human Immunodeficiency Virus Type 1 and 2 (HIV-1/HIV-2), Hepatitis A Virus (HAV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) or Parvovirus B19 -Negative at Baseline Who Are Seropositive for Any of These Viruses
Time frame: Up to Month 30
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jan 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Ken Woodward study director
Instituto Grifols SA
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Alphanate SD/HT in people with Severe Hemophilia A, run by Grifols Biologicals, LLC at 2 sites in Poland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Poland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Jun 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Factor VIII (FVIII) Inhibitor Development (time frame: Up to Month 30). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jan 2025.